1. Field of the Invention
This invention relates to novel organic compounds. More particularly, this invention relates to certain 2-(substituted anilino)benzoxazoles, compositions thereof, and methods for using same in suppressing the immune response mechanism, controlling fertility, improving weight gains and reducing gross lesions in chickens exposed to Marek's disease, and as herbicides.
2. Description of the Prior Art
Considerable interest has developed in recent years in the physiological activity of 2-substitutedbenzoxazoles. Some urea derivatives of this class of compounds are described in the art. For example, N-(benzoxazoyl)-N'-C.sub.1 -C.sub.5 aliphatic ureas are disclosed in U.S. Pat. No. 3,299,085 as intermediates in the preparation of certain herbicides. U.S. Pat. No. 3,162,644 describes 2-benzoxazoylureas useful as plant growth regulators and muscle relaxants. Paget, et al., have described the immunosuppressive activity of a number of benzoxazoleureas. [Paget, C. J.; Kisner, K.; Stone, R. L.; and DeLong, D. C.; J. Med. Chem., 12 1016 et seq. (1969)].
Deck, et al., reported the synthesis of 2-anilinobenzaxole [Deck and Dains, J. Amer. Chem. Soc., 55, 4986 (1933)].
Recently, immunosuppressive agents have come into prominence because of their use during organ transplants from one human to another, particularly in connection with heart and kidney transplants. It is part of the defense mechanism of humans to reject foreign antigens (in this case, the transplanted organ) by the immune reaction. Thus, in all of the organ transplant operations it has been necessary to give large doses of an immunosuppressive agent prior to the surgery and continuing thereafter in order to prevent the host from rejecting the donor organ. The present immunosuppressive agent of choice is azathioprine U.S. Pat. No. 3,056,785).
In addition, a significant emphasis is developing on the population explosion. More reliable fertility control agents are needed to be used in overcoming the sky-rocketing birth rate in many underdeveloped countries of the world. More to the point is the desire to perfect a method for preventing the development of the fertilized ova, a "morning after" contraceptive as it were.
Moreover, Marek's disease is a debilitating disease which attacks avian species and is found throughout the world wherever chickens are present. The causative agent is thought to be a virus or viruses of the herpes type. The mode of infection is believed to be through the breathing or ingestion of the virus or by transmission from the hen via the fertile egg to the embryo. The incubation period for the disease is from four to six weeks. The disease includes all acute forms of avian leukosis that are characterized by a proliferation of pleomorphic lymphocytes and plasma cells. The lesions can be found in the nervous system, the eyes, the viscera, the skeletal muscle, and the skin. Marek's disease syndrome is said by Burmester and Witter, An Outline of the Diseases of the Avian Leukosis Complex, Production Research Report No. 94, United States Department of Agriculture (USDA) (1966), to encompass such clinical conditions as fowl paralysis, range paralysis, polyneuritis, neurolymphomatosis gallinarum, visceral lymphomatosis, acute leukosis, ocular lymphomatosis and iritis. The early manifestations of the disease are apparent in such conditions as failure to gain weight, dehydration, and paralysis. The disease may result in an early or lingering death or, if the bird survives the acute phase of the disease, a regression of the symptoms may take place, and the bird may recover. However, even recovered birds can contribute to substantial economic losses to the grower because they fall behind in the growth schedule. The economic loss to the poultry industry from Marek's disease is high. For example, it has been estimated that the incidence of Marek's disease in broiler flocks ranges up to 8 percent. In 1968, about 36 million broiler chickens damaged by Marek's disease were condemned in USDA-inspected processing plants. This figure represented about 48 percent of all condemnations reported in 1968 (USDA Statistical Reporting Service POW 2-1, Crop Reporting Board, Washington, D.C. 20250).
Until a short time ago, control procedures for Marek's disease were limited to maintenance of good hygiene and sanitation and to the development of strains of disease-resistant birds. More recently a prophylactic vaccine has been announced which comprises the parenteral administration of a turkey virus found to be nonpathogenic to chickens. U.S. Pat. No. 3,548,054 claims the use of parenterally administered live attenuated Newcastle disease virus vaccine to young chicks up to the seventh day after hatching for improving weight gains and reducing gross lesions in chickens exposed to Marek's disease. U.S. patent application Ser. No. 831,229 discloses the use of Statolon as a parenterally administered substance for the improvement of weight gains and the reduction of gross lesions in chickens exposed to Marek's disease. There are no disclosed methods for altering the pathogenesis of Marek's disease by orally administering an agent for the prophylaxis or treatment of Marek's disease.
It is an object of this invention to provide compositions and methods for suppressing the immune reaction in warm-blooded mammals employing 2-(substituted anilino)benzoxazoles as active agents. It is another object of this invention to provide methods for controlling fertility by administering certain 2-(substituted anilino)benzoxazoles as active materials. It is a further object of this invention to provide compositions and methods for increasing weight gains and reducing gross lesions in chickens exposed to Marek's disease by employing certain 2-(substituted anilino)benzoxazoles as active compounds.